One important aspect of the human and animal immune system is the negative regulation of the immune responses that occur in response to the apparent presence of antigens. If no brake were placed on immune response, antibody-producing cells, for one example, would continue producing antibodies indefinitely. When the immune system is not appropriately regulated, several systemic malfunctions can occur. Defects of the operation of the immune system such as these have been associated with certain autoimmune disorders, in which the body reacts against its own tissue as if the tissue were a foreign body. Rheumatoid arthritis, multiple sclerosis, myasthenia gravis, lupus erythematosus, and insulin-dependent diabetes (type 1) are believed to be examples of such conditions.
The negative regulation of the immune system is believed to be controlled in part by cells known as "suppressor cells." Human suppressor cells include T8 cells (also known as T8.sup.+ cells); there may be other human suppressor cells. Suppressor cells act in concert with other cells to bring about a normal immune response, what may be considered immune system homeostasis. Autoimmune defects of the type described above may result from insufficient production, potentiation, or operation (which are collectively referred to at times hereinafter as "activation") of suppressor cells. It is therefore useful to assay suppressor cell function, and in particular to assay the maximum capacity of a suppressor cell population to be activated. However, convenient, inexpensive, in vitro diagnostic tests for diagnosing or assaying suppressor cell function are presently unavailable. In particular, quantitative tests are presently unavilable.
A copending patent application of the inventor (Gottlieb, "Diagnostic Methods for Immune Function," U.S. patent application Ser. No. 830,728, now issued as U.S. Pat. No. 4,778,750) describes a method for assaying amplifier immune reserve, a function of the human and animal immune system in some respects similar to that of the present invention. An abstract published in March 1985 (Sizemore, Farmer, and Gottlieb, "Enhancement of nonspecific suppressor T cell activity by immunomodulators derived from human leukocyte dialysates," Fed. Proceedings 947, No. 3133) refers in general terms to various aspects of the procedures described herein. Other background on amplifiers and suppressors is found in Gottlieb U.S. Pat. No. 4,468,379, in copending Gottlieb U.S. patent application Ser. No. 643,724 now issued as U.S. Pat. No. 4,616,099, and in copending Gottlieb U.S. patent application Ser. No. 813,632, now issued as U.S. Pat. No. 4,699,898.
A known method of cultivating suppressor cells is to expose normal lymphocytes to a plant product known as concanavalin A (Con A), which in certain concentrations induces the production of suppressor cells. By culturing lymphocytes with Con A, suppressor cells can be produced. See generally Shou, Schwartz, and Good, Suppressor cell activity after concanavalin A treatment of lymphocytes from normal donors, 143 J. Exp. Med. 1100 (1976); Birnbaum and Swick, Human suppressor lymphocytes, 40 Cell Immunol. 16 (1978). It is also known that proliferation of cells may be inhibited by administration of such agents as mitomycin, which interferes with cell division.